A Comprehensive Review on the Pleotropic Role of Nitric Oxide, a Well-Known Cytotoxin

Free radical nitric oxide (NO\(\bullet\)) plays a dual role in human physiology and pathophysiology. At low levels NO\(\bullet\) is considered to play a protective role for cells; however, at higher levels it becomes cytotoxic and contributes to tumor angiogenesis and cancer progression. Although earlier studies investigating the role of NO\(\bullet\) in cancer have been tissue-specific, this review focuses on the underlying similarities of NO\(\bullet\) exposure that present across a variety of site-specific cancers. We also try to explain the role of NO\(\bullet\)and the cellular protecting enzyme glutathione-transferase. This article emphasizes the emerging role of NO\(\bullet\)in three main areas related to epigenetics: DNA methylation, microRNAs, and histone modifications. In conclusion, we describe the recent advancement of a model cell line system in which cells demonstrate a high level of NO\(\bullet\) nitric oxide adaptation, and propose that these adapted cell lines can act as useful tools to study the role of NO\(\bullet\) in cancer biology.